A very simple model system, the cellular slime mold Dictyostelium discoideum, is being used to study mechanisms which control developmental gene activation during normal differentiation. Postaggregation Dictyostelium cells transcribe an additional 26% of their genome which is not expressed in earlier pre-aggregation stage cells. Cell-cell interaction is a necessary prerequisite for the synthesis and stability of these new differentiation-specific messenger RNAs. Additionally, the transcription rate and stability of these messenger RNAs are further regulated by a cyclic AMP-mediated process. We have demonstrated that 1) lyzosomatrophic agents such as (NH4)2S04 can replace the need for cell-cell interaction for postaggregation gene expression; 2) cAMP acts to regulate post aggregation gene expression through the cell surface cAMP receptor; 3) accumulation of mRNA for differentiation-specific genes expressed in prestalk cells is regulated though a different kinetic form of the cell surface receptor than those expressed in prespore cells; 4) activation of the cAMP receptor-associated adenylate cyclase does not play a role in the second messenger signal transduction system utilized for activation of expression of either the prespore or the prestalk genes; 5) prespore genes but not prestalk genes utilize a Ca++/Calmodulin-dependent second messenger signal transduction system for their activation; finally, 6) pathways that induce the expression of differentiation-specific genes in prespore cells suppress the expression of genes transcribed during growth.